Amino acid position 37 of HLA-DRβ1 affects susceptibility to Crohns disease in Asians

Han, Buhm; Akiyama, Masato; Kim, Kyung-Kon; Oh, Hyunjung; Choi, Hyunchul; Lee, Cue Hyunkyu; Jung, Seulgi; Lee, Ho-Su; Kim, Emma E.; Cook, Seungho; Haritunians, Talin; Yamazaki, Keiko; Park, Sang Hyoung; Ye, Byong Duk; McGovern, Dermot P. B.; Esaki, Motohiro; Kawaguchi, Takaaki; Khor, Seik-Soon; Taylor, Kent D.; Rotter, Jerome, I; Suzuki, Yasuo; Matsui, Toshiyuki; Motoya, Satoshi; Bang, So-Young; Kim, Tae-Hwan; Momozawa, Yukihide; Kamatani, Yoichiro; Tokunaga, Katsushi; Kubo, Michiaki; Okada, Yukinori; Yang, Suk-Kyun; Song, Kyuyoung

doi:10.1093/hmg/ddy285

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Amino acid position 37 of HLA-DRβ1 affects susceptibility to Crohns disease in Asians : Amino acid position 37 of HLA-DR beta 1 affects susceptibility to Crohn's disease in Asians

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Authors: Han, Buhm; Akiyama, Masato; Kim, Kyung-Kon; Oh, Hyunjung; Choi, Hyunchul; Lee, Cue Hyunkyu; Jung, Seulgi; Lee, Ho-Su; Kim, Emma E.; Cook, Seungho; Haritunians, Talin; Yamazaki, Keiko; Park, Sang Hyoung; Ye, Byong Duk; McGovern, Dermot P. B.; Esaki, Motohiro; Kawaguchi, Takaaki; Khor, Seik-Soon; Taylor, Kent D.; Rotter, Jerome, I; Suzuki, Yasuo; Matsui, Toshiyuki; Motoya, Satoshi; Bang, So-Young; Kim, Tae-Hwan; Momozawa, Yukihide; Kamatani, Yoichiro; Tokunaga, Katsushi; Kubo, Michiaki; Okada, Yukinori; Yang, Suk-Kyun; Song, Kyuyoung

Issue Date: 2018-11

Publisher: Oxford University Press

Citation: Human Molecular Genetics, Vol.27 No.22, pp.3901-3910

Abstract: Crohn's disease (CD) and ulcerative colitis (UC) are the major types of chronic inflammatory bowel disease (IBD) characterized by recurring episodes of inflammation of the gastrointestinal tract. Although it is well established that human leukocyte antigen (HLA) is a major risk factor for IBD, it is yet to be determined which HLA alleles or amino acids drive the risks of CD and UC in Asians. To define the roles of HLA for IBD in Asians, we fine-mapped HLA in 12 568 individuals from Korea and Japan (3294 patients with CD, 1522 patients with UC and 7752 controls). We identified that the amino acid position 37 of HLA-DR beta 1 plays a key role in the susceptibility to CD (presence of serine being protective, P = 3.6 x 10(-67), OR = 0.48 [0.45-0.52]). For UC, we confirmed the known association of the haplotype spanning HLA-C*12:02, HLA-B*52:01 and HLA-DRB1*1502 (P = 1.2 x 10(-28), OR = 4.01 [3.14-5.12]).